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Selective vulnerability in striosomes and in the nigrostriatal dopaminergic pathway after methamphetamine administration : early loss of TH in striosomes after methamphetamine.

Granado N, Ares-Santos S, O'Shea E, Vicario-Abejón C, Colado MI, Moratalla R - Neurotox Res (2009)

Bottom Line: In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals.Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix.In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens.

View Article: PubMed Central - PubMed

Affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avda. Dr. Arce 37, 28002, Madrid, Spain.

ABSTRACT
Methamphetamine (METH), a commonly abused psychostimulant, causes dopamine neurotoxicity in humans, rodents, and nonhuman primates. This study examined the selective neuroanatomical pattern of dopaminergic neurotoxicity induced by METH in the mouse striatum. We examined the effect of METH on tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the different compartments of the striatum and in the nucleus accumbens. The levels of dopamine and its metabolites, 3,4-dihidroxyphenylacetic acid and homovanillic acid, as well as serotonin (5-HT) and its metabolite, 5-hydroxyindolacetic acid, were also quantified in the striatum. Mice were given three injections of METH (4 mg/kg, i.p.) at 3 h intervals and sacrificed 7 days later. This repeated METH injection induced a hyperthermic response and a decrease in striatal concentrations of dopamine and its metabolites without affecting 5-HT concentrations. In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals. Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix. The predominant loss of dopaminergic terminals in the striosomes occurred along the rostrocaudal axis of the striatum. In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens. These results provide the first evidence that compartments of the mouse striatum, striosomes and matrix, and mesolimbic and nigrostriatal pathways have different vulnerability to METH. This pattern is similar to that observed with other neurotoxins such as MPTP, the most widely used model of Parkinson's disease, in early Huntington's disease and hypoxic/ischemic injury, suggesting that these conditions might share mechanisms of neurotoxicity.

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Effect of METH on the striatal content of DA, DOPAC, and HVA. Amine levels were measured by HPLC in homogenates from striata of mice treated with METH (4 mg/kg) or saline. Mice were sacrificed 7 days after drug administration. Data represent the mean ± SEM, n = 6 animals/group. * 0.001 compared with control animals
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Fig6: Effect of METH on the striatal content of DA, DOPAC, and HVA. Amine levels were measured by HPLC in homogenates from striata of mice treated with METH (4 mg/kg) or saline. Mice were sacrificed 7 days after drug administration. Data represent the mean ± SEM, n = 6 animals/group. * 0.001 compared with control animals

Mentions: Seven days after METH administration (4 mg/kg, three times at 3 h intervals), there was a reduction (76%) in the striatal dopamine content (ng/g tissue) of METH-treated mice compared to saline (P < 0.001). The metabolites of dopamine, DOPAC and HVA, were also affected by treatment with METH. DOPAC was reduced by 64% (P < 0.001) and HVA levels by 59% (P < 0.001) in the METH-treated mice (Fig. 6). There were no differences between METH- and saline-treated animals in striatal 5-HT concentration or 5-HIAA concentration (P = 0.67 and P = 0.63, respectively) (Fig. 6).Fig. 6


Selective vulnerability in striosomes and in the nigrostriatal dopaminergic pathway after methamphetamine administration : early loss of TH in striosomes after methamphetamine.

Granado N, Ares-Santos S, O'Shea E, Vicario-Abejón C, Colado MI, Moratalla R - Neurotox Res (2009)

Effect of METH on the striatal content of DA, DOPAC, and HVA. Amine levels were measured by HPLC in homogenates from striata of mice treated with METH (4 mg/kg) or saline. Mice were sacrificed 7 days after drug administration. Data represent the mean ± SEM, n = 6 animals/group. * 0.001 compared with control animals
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875475&req=5

Fig6: Effect of METH on the striatal content of DA, DOPAC, and HVA. Amine levels were measured by HPLC in homogenates from striata of mice treated with METH (4 mg/kg) or saline. Mice were sacrificed 7 days after drug administration. Data represent the mean ± SEM, n = 6 animals/group. * 0.001 compared with control animals
Mentions: Seven days after METH administration (4 mg/kg, three times at 3 h intervals), there was a reduction (76%) in the striatal dopamine content (ng/g tissue) of METH-treated mice compared to saline (P < 0.001). The metabolites of dopamine, DOPAC and HVA, were also affected by treatment with METH. DOPAC was reduced by 64% (P < 0.001) and HVA levels by 59% (P < 0.001) in the METH-treated mice (Fig. 6). There were no differences between METH- and saline-treated animals in striatal 5-HT concentration or 5-HIAA concentration (P = 0.67 and P = 0.63, respectively) (Fig. 6).Fig. 6

Bottom Line: In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals.Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix.In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens.

View Article: PubMed Central - PubMed

Affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avda. Dr. Arce 37, 28002, Madrid, Spain.

ABSTRACT
Methamphetamine (METH), a commonly abused psychostimulant, causes dopamine neurotoxicity in humans, rodents, and nonhuman primates. This study examined the selective neuroanatomical pattern of dopaminergic neurotoxicity induced by METH in the mouse striatum. We examined the effect of METH on tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the different compartments of the striatum and in the nucleus accumbens. The levels of dopamine and its metabolites, 3,4-dihidroxyphenylacetic acid and homovanillic acid, as well as serotonin (5-HT) and its metabolite, 5-hydroxyindolacetic acid, were also quantified in the striatum. Mice were given three injections of METH (4 mg/kg, i.p.) at 3 h intervals and sacrificed 7 days later. This repeated METH injection induced a hyperthermic response and a decrease in striatal concentrations of dopamine and its metabolites without affecting 5-HT concentrations. In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals. Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix. The predominant loss of dopaminergic terminals in the striosomes occurred along the rostrocaudal axis of the striatum. In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens. These results provide the first evidence that compartments of the mouse striatum, striosomes and matrix, and mesolimbic and nigrostriatal pathways have different vulnerability to METH. This pattern is similar to that observed with other neurotoxins such as MPTP, the most widely used model of Parkinson's disease, in early Huntington's disease and hypoxic/ischemic injury, suggesting that these conditions might share mechanisms of neurotoxicity.

Show MeSH
Related in: MedlinePlus